The objective of this research project is to carry out a systematic evaluation of the changes that occur with aging in the hormonal regulation of plasma calcium concentration. The hypothesis to be tested is that calcium homeostatic control mechanisms will be modified by aging processes because of changes, (1) in the circulating levels of calcium regulating hormones, (2) in the sensitivity of the target tissues to their respective hormones, and (3) as a result of differences in sex. To evaluate these we shall carry out specific studies designed to: (a) clarify the physiological significance of calcitonin in the control of calcium homeostasis, (b) determine whether the relative contributions of calcitonin and parathyroid hormone to the maintenance of normocalcemia alter with aging, (c) assess whether any changes in the relative roles of these hormones in the regulation of plasma calcium concentration are due to alterations with aging in: (1) the rate of bone turnover, (2) the response of the target organs to their respective hormones, and/or (3) the degradation rates of these hormones, and (d) determine the nature of the interrelationship between ovarian hormones and parathyroid hormone and calcitonin. Results obtained from these studies are of particular importance in three respects: first, they will contribute in clarifying the physiologic significance of calcitonin; secondly, they will help in identifying hitherto unappreciated alterations that occur with aging in the regulation of calcium metabolism; thirdly, they will enhance our understanding of the basis for some of the known alterations that occur with aging in calcium metabolism; fourthly, they will provide data that will form the background for an in-depth study of several aspects of age-related alterations in the control of calcium metabolism including, for example, a more detailed exploration of the interrelationship between sex hormones, calcium regulating hormones, aging and calcium and skeletal metabolism.